Texas Star-SR, an A-B+ mutant derived by nitrosoguanidine treatment from Vibrio cholerae El Tor Ogawa strain 3083, was fed to 68 volunteers as an oral vaccine in doses of 105 to 5 x 1010 organisms with NaHCO3. Sixteen (24%) vaccinees experienced some loose stools (unrelated to vaccine dose), but in only one did the total stool volume exceed 1.0 liter. The vaccine strain was cultured from duodenal fluid of 35 of 46 (76%) persons who ingested doses of 108 organisms or greater. No A+B+ toxinogenic revertants were found among 456 clinical isolates tested. Sixty-three vaccinees (93%) manifested seroconversions of vibriocidal antibody, whereas only 20 (29%) had significant rises in serum antitoxin titers. Paired intestinal fluids from 41 volunteers showed significant rises of secretory immunoglobulin A against lipopolysaccharide (29%), Ogawa outer membrane preparation (29%), and toxin (12%) antigens. In challenge studies with pathogenic V. cholerae El Tor Ogawa and El Tor Inaba, the attack rate in vaccinees (7 of 25) was significantly lower than in controls (18 of 25) (vaccine efficacy, 61%); furthermore, the diarheal stool volume in vaccinees was significantly less than that in controls (P < 0.01). Texas Star-SR served as a prototype to investigate the concept of immunoprophylaxis by means of attenuated strains as oral vaccines. These observations provide an invaluable background for planning future studies with newly developed attenuated strains prepared by recombinant DNA techniques.